Triamino pyrimidines and pyridines as histamine H(4) receptor modulators.

abstract：:We report an efficient approach for the chemical synthesis of Rhesus θ-defensin-1 (RTD-1) using Fmoc-based solid-phase peptide synthesis in combination with an intramolecular version of native chemical ligation. The corresponding linear thioester precursor was cyclized and folded in a one-pot reaction using reduced gl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aboye TL,Li Y,Majumder S,Hao J,Shekhtman A,Camarero JA

更新日期：2012-04-15 00:00:00

abstract：:A series of cis-2,6-dialkyl-4-chloro-tetrahydropyrans were prepared by means of an iron(III)-catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, SW1573, and WiDr. The results show that the presence of bulky substituents favors the Prins cyclization lead...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miranda PO,León LG,Martín VS,Padrón JI,Padrón JM

更新日期：2006-06-15 00:00:00

abstract：:A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Webster SP,Ward P,Binnie M,Craigie E,McConnell KM,Sooy K,Vinter A,Seckl JR,Walker BR

更新日期：2007-05-15 00:00:00

abstract：:Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu C,Yin Y,Meng F,Dun Y,Pei K,Wang C,Xu X,Wu F

更新日期：2018-06-15 00:00:00

abstract：:Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu GH,Gu M,Cassel JA,Belanger S,Graczyk TM,DeHaven RN,Conway-James N,Koblish M,Little PJ,DeHaven-Hudkins DL,Dolle RE

更新日期：2005-12-01 00:00:00

abstract：:Water is an essential part of protein binding sites and mediates interactions to ligands. Its displacement by ligand parts affects the free binding energy of resulting protein-ligand complexes. Therefore the characterization of solvation properties is important for design. Of particular interest is the propensity of l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matter H,Güssregen S

更新日期：2018-08-01 00:00:00

abstract：:Here we report a number of novel JS-K structural analogues with sub-micromolar anti-proliferative activities against human leukemia cell lines HL-60 and U937; JS-K is the anti-cancer lead compound O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. The ability of these compounds to g...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nandurdikar RS,Maciag AE,Citro ML,Shami PJ,Keefer LK,Saavedra JE,Chakrapani H

更新日期：2009-05-15 00:00:00

abstract：:Modulating the structural dynamics of biomembranes by inducing bilayer curvature and lipid packing defects has been highlighted as a practical tool to modify membrane-dependent cellular processes. Previously, we have reported on an amphipathic helical peptide derived from the N-terminal segment (residues 1-18, EpN18) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsu WY,Masuda T,Afonin S,Sakai T,Arafiles JVV,Kawano K,Hirose H,Imanishi M,Ulrich AS,Futaki S

更新日期：2020-06-15 00:00:00

abstract：:This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [(35)S]GTPgammaS to different subtypes of Gi protein. The problem arose from the strong affinity between [(35)S]GTPgammaS and the tested compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Manetti D,Di Cesare Mannelli L,Dei S,Guandalini L,Martini E,Banchelli M,Ghelardini C

更新日期：2009-04-15 00:00:00

abstract：:The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhai W,Flynn N,Longhi DA,Tino JA,Murphy BJ,Slusarchyk D,Gordon DA,Pendri A,Shi S,Stoffel R,Ma B,Sofia MJ,Gerritz SW

更新日期：2008-09-15 00:00:00

abstract：:A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Tang F,Huang W,Jin Q,Shen H,Wei P

更新日期：2013-10-15 00:00:00

abstract：:A series of substituted biphenyl ethylene ether compounds has been designed to target the gp41N-trimer in order to inhibit formation of the six-helical bundle that represents the end state of gp41-mediated viral fusion. A size exclusion HPLC based helical bundle formation (HBF) assay was developed to evaluate in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu B,Joseph RW,Dorsey BD,Schiksnis RA,Northrop K,Bukhtiyarova M,Springman EB

更新日期：2009-10-01 00:00:00

abstract：:A short route to pyrimidine locked nucleosides has been developed for their incorporation in triplex forming oligonucleotides (TFO). Compared to oligonucleotides built with standard nucleosides, the modified TFOs containing 3'-endo blocked residues formed, with their corresponding DNA duplexes, more stable triple heli...

journal_title：Bioorganic & medicinal chemistry letters

authors： Savy P,Benhida R,Fourrey JL,Maurisse R,Sun JS

更新日期：2000-10-16 00:00:00

abstract：:A modified vancomycin binding pocket (D-O-E ring) incorporating an alpha-hydroxy-beta-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 microg/ml against VREF). Both the lipidated aminoglucose and the struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jia Y,Gonzalez-Zamora E,Ma N,Liu Z,Bois-Choussy M,Malabarba A,Brunati C,Zhu J

更新日期：2005-10-15 00:00:00

abstract：:On-resin macrocyclization via an SNAr reaction is employed in the synthesis of tocinoic acid analogs. Specifically, an N-terminal nitrofluorobenzene is attacked by a nucleophilic C-terminal sidechain. The remaining nitro group can be reduced and acylated. NMR is used to compare the conformation of the new macrocyclic ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fotsch C,Kumaravel G,Sharma SK,Wu AD,Gounarides JS,Nirmala NR,Petter RC

更新日期：1999-08-02 00:00:00

abstract：:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key anal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

更新日期：2012-01-01 00:00:00

abstract：:Two new oligostilbenes, caragasinins A (5) and B (10), and eight known compounds, kobophenol A (1), (+)-α-viniferin (2), (+)-ampelopsin F (3), pallidol (4), (+)-isoampelopsin F (6), miyabenol C (7), carasinaurone (8) and caraphenol B (9) were isolated from the ethylacetate-soluble extract of the roots of Caragana sini...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin Q,Han XH,Hong SS,Lee C,Choe S,Lee D,Kim Y,Hong JT,Lee MK,Hwang BY

更新日期：2012-01-15 00:00:00

abstract：:New chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives have been synthesized by domino aldol-type reaction/hetero Diels-Alder reaction generated from o-quinone methide in situ from 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones with resorcinols/naphthols in the presenc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Madda J,Venkatesham A,Naveen Kumar B,Nagaiah K,Sujitha P,Ganesh Kumar C,Rao TP,Jagadeesh Babu N

更新日期：2014-09-15 00:00:00

abstract：:A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

更新日期：2009-07-01 00:00:00

abstract：:A three-step protocol for SAR development was introduced and applied to the SAR studies of the MK2 inhibitor program. Following this protocol, key conformational features and functional groups for improving MK2 inhibitor activity were quickly identified. Through this effort, the initial gap observed between in vitro b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang X,Zhu X,Chen X,Zhou W,Xiao D,Degrado S,Aslanian R,Fossetta J,Lundell D,Tian F,Trivedi P,Palani A

更新日期：2012-01-01 00:00:00

abstract：:A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gong L,Han X,Silva T,Tan YC,Goyal B,Tivitmahaisoon P,Trejo A,Palmer W,Hogg H,Jahagir A,Alam M,Wagner P,Stein K,Filonova L,Loe B,Makra F,Rotstein D,Rapatova L,Dunn J,Zuo F,Dal Porto J,Wong B,Jin S,Chang A,T

更新日期：2013-06-15 00:00:00

abstract：:Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Petrov KG,Zhang YM,Carter M,Cockerill GS,Dickerson S,Gauthier CA,Guo Y,Mook RA Jr,Rusnak DW,Walker AL,Wood ER,Lackey KE

更新日期：2006-09-01 00:00:00

abstract：:Bromofluoroacetophenone derivatives which produce fluorine substituted phenyl radicals that cleave DNA upon excitation were investigated as a novel photonuclease. Pyrrolecarboxamide-conjugated bromofluoroacetophenones; 4'-bromo-2'-fluoroacetophenone and 2'-bromo-4'-fluoroacetophenone were synthesized and their DNA cle...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wender PA,Jeon R

更新日期：2003-05-19 00:00:00

abstract：:Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nano...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang G,Madan D,Prestwich GD

更新日期：2011-09-01 00:00:00

abstract：:The growth inhibition of human cancer cells via T-type Ca(2+) channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca(2+) channel (Cav3.1) blockade and cytotoxicity on three human ovari...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jang SJ,Choi HW,Choi DL,Cho S,Rim HK,Choi HE,Kim KS,Huang M,Rhim H,Lee KT,Lee JY

更新日期：2013-12-15 00:00:00

abstract：:A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety or at the cationic head or at both, were tested for binding affinity at muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic affinity was found, submicromolar Ki values, similar to that of carbachol, were measured at α...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bolchi C,Valoti E,Binda M,Fasoli F,Ferrara R,Fumagalli L,Gotti C,Matucci R,Vistoli G,Pallavicini M

更新日期：2013-12-01 00:00:00

abstract：:A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewis TA,Young MA,Arrington MP,Bayless L,Cai X,Collart P,Eckman JB,Ellis JL,Ene DG,Libertine L,Nicolas JM,Scannell RT,Wels BF,Wenberg K,Wypij DM

更新日期：2004-11-15 00:00:00

abstract：:A series of cysteine diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low mi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perrey DA,Narla RK,Uckun FM

更新日期：2000-03-20 00:00:00

abstract：:On the search for anti-cancer compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the rhizomes of Acorus gramineus resulted in the isolation and identification of thirteen phenolic derivatives (1-13) including two new 8-O-4'-neolignans, n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim KH,Moon E,Kim HK,Oh JY,Kim SY,Choi SU,Lee KR

更新日期：2012-10-01 00:00:00

abstract：:We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang S,Jia XD,Liu ML,Lu Y,Guo HY

更新日期：2012-09-15 00:00:00